Abstract
1372
Objectives To study the biodistribution, pharmacokinetics, and toxicity of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. This phase I trial provides IP therapy for patients with HER-2-expressing peritoneal carcinomatosis who have failed standard therapies.
Methods IP 212Pb-TCMC-trastuzumab was delivered IP <4h after 4mg/kg IV trastuzumab.
Results Serial planar imaging studies in the first cohort (n=3) show little redistribution of radioactivity out of the peritoneal cavity and no significant uptake in major organs including heart. The ratio of chest region of interest to that of the whole body was 0.11-0.13 compared to 0.48-0.53for the abdomen vs. whole body. Non-decay corrected cumulative urinary excretion was < 6% in 24 h (2.3 half lives). Peak blood activity was 6.3nCi/ml at 18 h, and maximum blood concentration of the radiolabeled antibody was seen at 63 h with a maximum of 23% injected dose of antibody conjugate based on decay corrected values. External radiation dose-rate measurements were made at four positions over 24 h to assess retention half-time and biodistribution. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67mR/h and dropped to 0.67mR/h by 24hours. The exposure rates at the other positions monitored (axilla, chest, femur) were proportional to distance from the abdomen. The ratio of the average exposure rates at the abdomen over other sites was 2-12.8 post-infusion and changed to 1.3-5.9 by 24 h, consistent with modest re-distribution. The data points correlate closely with 212Pb physical decay (T1/2 =10.6 h). Patients tolerated therapy at 0.2 mCi/m2 (7.4 MBq/m2) with no evidence of marrow suppression, cardiac, liver or renal toxicity.
Conclusions First cohort 212Pb-TCMC-trastuzumab IP treatment of patients with peritoneal carcinomatosis showed minimal distribution outside the peritoneal cavity with little detectable organ uptake, <6 % urinary excretion, and good tolerance without related toxicity.
Research Support ArevaMed, NIH 1UL1RR025777-01